Skin cancer is the most common of all cancers and melanoma is a deadly skin cancer that accounts for over 75% of all the skin cancer deaths in the United States. The incidence of melanoma is rising at approximately 3% per year. Early detection of melanoma results in 95% cure rate. But, early detection of melanoma is difficult because of the subtle changes that differentiate a malignant melanoma from a benign mole. Better methods to detect these subtle changes, and more frequent screening for skin cancer, will significantly improve the early detection of melanoma and possibly reduce the number of deaths caused by this disease. Early detection of melanoma requires better methods for examining subtle changes in the pigmentation of the suspicious moles. Side-transillumination, whereby light is directed into the skin from around the suspicious mole, is a new method that makes the skin translucent so that the subsurface structures can be examined with clarity. This technique is used in a prototype device called the Nevoscope and has the potential for improving the early detection of skin cancers such as melanoma and basal cell carcinoma. The goal of this research project is to validate the use of side-transillumination for the detection of melanoma by comparing its detection accuracy to the established oil epiluminescence method. The second goal of the research project is to develop a commercial model of the Nevoscope for clinical use by the dermatologists that would be easy to use and affordable. The clinical validation study will digitally image 240 skin lesions suspicious for malignancy using the oil-based imaging and the side-transillumination imaging in the same lesion. Two dermatologists that are blinded to the patient history, and who will make a diagnosis based on a semi quantitative scoring method, will read these images. Diagnostic accuracy for melanoma will be computed for the two methods based on pathology-determined diagnosis of the excised lesion. The long-term goal of this research is to validate the side-transillumination method and develop the Nevoscope device into a commercial product for improved early diagnoses of skin cancers.